Genome-wide association study implicates CHRNA2 in cannabis use disorder

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Genome-wide association study implicates CHRNA2 in cannabis use disorder. / Demontis, Ditte; Rajagopal, Veera Manikandan; Thorgeirsson, Thorgeir E.; Als, Thomas D.; Grove, Jakob; Leppälä, Kalle; Gudbjartsson, Daniel F.; Pallesen, Jonatan; Hjorthøj, Carsten; Reginsson, Gunnar W.; Tyrfingsson, Thorarinn; Runarsdottir, Valgerdur; Qvist, Per; Christensen, Jane Hvarregaard; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Marie; Huckins, Laura M.; Stahl, Eli A.; Timmermann, Allan; Agerbo, Esben; Hougaard, David M.; Werge, Thomas; Mors, Ole; Mortensen, Preben Bo; Nordentoft, Merete; Daly, Mark J.; Stefansson, Hreinn; Stefansson, Kari; Nyegaard, Mette; Børglum, Anders D.

In: Nature Neuroscience, Vol. 22, 06.2019, p. 1066-1074.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Demontis, D, Rajagopal, VM, Thorgeirsson, TE, Als, TD, Grove, J, Leppälä, K, Gudbjartsson, DF, Pallesen, J, Hjorthøj, C, Reginsson, GW, Tyrfingsson, T, Runarsdottir, V, Qvist, P, Christensen, JH, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Huckins, LM, Stahl, EA, Timmermann, A, Agerbo, E, Hougaard, DM, Werge, T, Mors, O, Mortensen, PB, Nordentoft, M, Daly, MJ, Stefansson, H, Stefansson, K, Nyegaard, M & Børglum, AD 2019, 'Genome-wide association study implicates CHRNA2 in cannabis use disorder', Nature Neuroscience, vol. 22, pp. 1066-1074. https://doi.org/10.1038/s41593-019-0416-1

APA

Demontis, D., Rajagopal, V. M., Thorgeirsson, T. E., Als, T. D., Grove, J., Leppälä, K., Gudbjartsson, D. F., Pallesen, J., Hjorthøj, C., Reginsson, G. W., Tyrfingsson, T., Runarsdottir, V., Qvist, P., Christensen, J. H., Bybjerg-Grauholm, J., Bækvad-Hansen, M., Huckins, L. M., Stahl, E. A., Timmermann, A., ... Børglum, A. D. (2019). Genome-wide association study implicates CHRNA2 in cannabis use disorder. Nature Neuroscience, 22, 1066-1074. https://doi.org/10.1038/s41593-019-0416-1

CBE

Demontis D, Rajagopal VM, Thorgeirsson TE, Als TD, Grove J, Leppälä K, Gudbjartsson DF, Pallesen J, Hjorthøj C, Reginsson GW, Tyrfingsson T, Runarsdottir V, Qvist P, Christensen JH, Bybjerg-Grauholm J, Bækvad-Hansen M, Huckins LM, Stahl EA, Timmermann A, Agerbo E, Hougaard DM, Werge T, Mors O, Mortensen PB, Nordentoft M, Daly MJ, Stefansson H, Stefansson K, Nyegaard M, Børglum AD. 2019. Genome-wide association study implicates CHRNA2 in cannabis use disorder. Nature Neuroscience. 22:1066-1074. https://doi.org/10.1038/s41593-019-0416-1

MLA

Vancouver

Author

Demontis, Ditte ; Rajagopal, Veera Manikandan ; Thorgeirsson, Thorgeir E. ; Als, Thomas D. ; Grove, Jakob ; Leppälä, Kalle ; Gudbjartsson, Daniel F. ; Pallesen, Jonatan ; Hjorthøj, Carsten ; Reginsson, Gunnar W. ; Tyrfingsson, Thorarinn ; Runarsdottir, Valgerdur ; Qvist, Per ; Christensen, Jane Hvarregaard ; Bybjerg-Grauholm, Jonas ; Bækvad-Hansen, Marie ; Huckins, Laura M. ; Stahl, Eli A. ; Timmermann, Allan ; Agerbo, Esben ; Hougaard, David M. ; Werge, Thomas ; Mors, Ole ; Mortensen, Preben Bo ; Nordentoft, Merete ; Daly, Mark J. ; Stefansson, Hreinn ; Stefansson, Kari ; Nyegaard, Mette ; Børglum, Anders D. / Genome-wide association study implicates CHRNA2 in cannabis use disorder. In: Nature Neuroscience. 2019 ; Vol. 22. pp. 1066-1074.

Bibtex

@article{01ae5cc4e42442debb86abd87da26cf7,
title = "Genome-wide association study implicates CHRNA2 in cannabis use disorder",
abstract = "Cannabis is the most frequently used illicit psychoactive substance worldwide; around one in ten users become dependent. The risk for cannabis use disorder (CUD) has a strong genetic component, with twin heritability estimates ranging from 51 to 70%. Here we performed a genome-wide association study of CUD in 2,387 cases and 48,985 controls, followed by replication in 5,501 cases and 301,041 controls. We report a genome-wide significant risk locus for CUD (P = 9.31 × 10−12) that replicates in an independent population (Preplication = 3.27 × 10−3, Pmeta-analysis = 9.09 × 10−12). The index variant (rs56372821) is a strong expression quantitative trait locus for cholinergic receptor nicotinic α2 subunit (CHRNA2); analyses of the genetically regulated gene expression identified a significant association of CHRNA2 expression with CUD in brain tissue. At the polygenic level, analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance. The results provide biological insights and inform on the genetic architecture of CUD.",
keywords = "ACTIVATION, HERITABILITY, LOCI, MARIJUANA USE, METAANALYSIS, NICOTINE, POLYGENIC RISK, PSYCHIATRIC-DISORDERS, SCHIZOPHRENIA, USE INITIATION",
author = "Ditte Demontis and Rajagopal, {Veera Manikandan} and Thorgeirsson, {Thorgeir E.} and Als, {Thomas D.} and Jakob Grove and Kalle Lepp{\"a}l{\"a} and Gudbjartsson, {Daniel F.} and Jonatan Pallesen and Carsten Hjorth{\o}j and Reginsson, {Gunnar W.} and Thorarinn Tyrfingsson and Valgerdur Runarsdottir and Per Qvist and Christensen, {Jane Hvarregaard} and Jonas Bybjerg-Grauholm and Marie B{\ae}kvad-Hansen and Huckins, {Laura M.} and Stahl, {Eli A.} and Allan Timmermann and Esben Agerbo and Hougaard, {David M.} and Thomas Werge and Ole Mors and Mortensen, {Preben Bo} and Merete Nordentoft and Daly, {Mark J.} and Hreinn Stefansson and Kari Stefansson and Mette Nyegaard and B{\o}rglum, {Anders D.}",
year = "2019",
month = jun,
doi = "10.1038/s41593-019-0416-1",
language = "English",
volume = "22",
pages = "1066--1074",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Genome-wide association study implicates CHRNA2 in cannabis use disorder

AU - Demontis, Ditte

AU - Rajagopal, Veera Manikandan

AU - Thorgeirsson, Thorgeir E.

AU - Als, Thomas D.

AU - Grove, Jakob

AU - Leppälä, Kalle

AU - Gudbjartsson, Daniel F.

AU - Pallesen, Jonatan

AU - Hjorthøj, Carsten

AU - Reginsson, Gunnar W.

AU - Tyrfingsson, Thorarinn

AU - Runarsdottir, Valgerdur

AU - Qvist, Per

AU - Christensen, Jane Hvarregaard

AU - Bybjerg-Grauholm, Jonas

AU - Bækvad-Hansen, Marie

AU - Huckins, Laura M.

AU - Stahl, Eli A.

AU - Timmermann, Allan

AU - Agerbo, Esben

AU - Hougaard, David M.

AU - Werge, Thomas

AU - Mors, Ole

AU - Mortensen, Preben Bo

AU - Nordentoft, Merete

AU - Daly, Mark J.

AU - Stefansson, Hreinn

AU - Stefansson, Kari

AU - Nyegaard, Mette

AU - Børglum, Anders D.

PY - 2019/6

Y1 - 2019/6

N2 - Cannabis is the most frequently used illicit psychoactive substance worldwide; around one in ten users become dependent. The risk for cannabis use disorder (CUD) has a strong genetic component, with twin heritability estimates ranging from 51 to 70%. Here we performed a genome-wide association study of CUD in 2,387 cases and 48,985 controls, followed by replication in 5,501 cases and 301,041 controls. We report a genome-wide significant risk locus for CUD (P = 9.31 × 10−12) that replicates in an independent population (Preplication = 3.27 × 10−3, Pmeta-analysis = 9.09 × 10−12). The index variant (rs56372821) is a strong expression quantitative trait locus for cholinergic receptor nicotinic α2 subunit (CHRNA2); analyses of the genetically regulated gene expression identified a significant association of CHRNA2 expression with CUD in brain tissue. At the polygenic level, analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance. The results provide biological insights and inform on the genetic architecture of CUD.

AB - Cannabis is the most frequently used illicit psychoactive substance worldwide; around one in ten users become dependent. The risk for cannabis use disorder (CUD) has a strong genetic component, with twin heritability estimates ranging from 51 to 70%. Here we performed a genome-wide association study of CUD in 2,387 cases and 48,985 controls, followed by replication in 5,501 cases and 301,041 controls. We report a genome-wide significant risk locus for CUD (P = 9.31 × 10−12) that replicates in an independent population (Preplication = 3.27 × 10−3, Pmeta-analysis = 9.09 × 10−12). The index variant (rs56372821) is a strong expression quantitative trait locus for cholinergic receptor nicotinic α2 subunit (CHRNA2); analyses of the genetically regulated gene expression identified a significant association of CHRNA2 expression with CUD in brain tissue. At the polygenic level, analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance. The results provide biological insights and inform on the genetic architecture of CUD.

KW - ACTIVATION

KW - HERITABILITY

KW - LOCI

KW - MARIJUANA USE

KW - METAANALYSIS

KW - NICOTINE

KW - POLYGENIC RISK

KW - PSYCHIATRIC-DISORDERS

KW - SCHIZOPHRENIA

KW - USE INITIATION

UR - http://www.scopus.com/inward/record.url?scp=85067847434&partnerID=8YFLogxK

U2 - 10.1038/s41593-019-0416-1

DO - 10.1038/s41593-019-0416-1

M3 - Journal article

C2 - 31209380

AN - SCOPUS:85067847434

VL - 22

SP - 1066

EP - 1074

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

ER -